The invention relates generally to a combination of dietary supplements for preventing migraine headaches. More particularly, the invention relates to a combination of dietary supplements and a method of treatment with the combination of dietary supplements for preventing and reducing an occurrence of a migraine headache and a plurality of associated symptoms of migraine headaches.
Migraine is a potentially chronic, progressive and pervasive disease that erodes the sufferer's daily quality of life and as well as substantially affecting patients' families, workplaces and society. Historically, migraine has been characterized as episodic attacks separated by normal, symptom-free periods. Findings from migraine sufferers surveyed in a national poll revealed that migraineurs do not view their migraines as isolated events. These sufferers consider their migraines part of a cycle of suffering, treating their current attack and worrying about when the next attack will strike. (J. L. Brandes, Headache: The Journal of Head and Face Pain; Vol. 48, p. 430-441, March 2008)
Migraines are more prevalent in women than men at almost a three to one ratio, associated with mainly the hormone milieu of the reproductive years. The overwhelming majority, more than four-fifths of self-diagnosed or physician diagnosed sufferers of “sinus” headaches actually meet the criteria for migraine headaches. Migraine is under-recognized and under diagnosed. (Curtis Schreiber et al., Archives Int. Med. Vol. 164, No. 16, Sep. 13, 2004)
The medical community, in recognizing the chronic and progressive nature of migraine, can focus on prevention or reversal of disease progression. Less than five percent of migraine sufferers receive preventive therapy. Most in-office visits do not result in significant information exchanged between doctor and patient about the severity of headaches or the degree of impairment. Candidates for preventive therapy often leave office without discussion or receiving preventive medication. (Richard B. Lipton et al., J. Gen Intern Med. 2008 August; 23(8): 1145-1151.) Non-pharmacological prevention focuses on avoiding migraine food triggers, a healthy lifestyle with adequate sleep and exercise, biofeedback and relaxation. Preventive medications that the Food and Drug Administration has approved include antiepileptic drugs topiramate and divalproate sodium for migraine prophylaxis. However, other antiepileptic drugs do not work and are not approved for this indication. (Roger Cady, Mayo Clin. Proc., May 2009; 84(5):397-399) Another approach to prophylaxis is the use of botulinum toxin, which incurs minimal systemic side effects and does not rely on daily patient compliance. Botulinum toxin was discovered to have a high affinity to the neuromuscular junction, inhibiting release of adenosine. Botulinum toxin Type A was reported in reducing the number of headache days in patients.
Efficacy of preventive therapy is defined as greater than a fifty percent reduction in migraine frequency. Fifty percent of patients do not respond to preventive medication. Beneficial effects of preventive medication may be reduced by abuse of other medications during treatment of an acute attack. (Beverly Tozer et al., Mayo Clin. Proc., August 2006; 81(8):1086-1092)
Effective migraine preventive therapy should decrease the frequency, severity, and duration of migraines, thereby helping to less the cycle of migraine and possibly prevent or reduce chronicity. Patients receiving drug prophylaxis had lower migraine-related costs than using acute treatment alone. A large segment of patients remain under-treated. (Brandes, Id.)
Migraine is also associated with both comorbid and concomitant illnesses that influence treatment strategy. Comorbid illness include depression, anxiety, epilepsy, sleep disorders, stroke; concomitant disorders include hypertension and obesity. Polytherapy, that is treating each disorder as a separate indication, increases the likelihood and the danger of interactions. Patients are not accepting of side effects from multiple medications and drop one or more drugs from their regimen. Monotherapy, that is a single agent that covers migraine and comorbid conditions, requires choosing the right drug, dosage and regimen, which may result in a less than effective migraine preventive treatment method.
Drugs approved for migraine prophylaxis include the beta blockers propranolol and timolol and the antiepileptic drugs divalproex and topiramate discussed previously. Drugs used off-label for prophylaxis include other agents of the beta blocker and anticonvulsant classes, calcium channel blockers, and antidepressants (e.g., tricyclics and selective serotonin re-uptake inhibitors). (Lawrence D. Goldberg; Am J Manag Care. 2005; 11:S62-S67)
Several theories have been proposed for the etiology of migraine headaches. One theory, dating back to 1938 from Graham and Wolff attribute migraines to vasoconstriction followed by vasodilation. Modern blood flow imaging techniques have shown that this does not fit the typical course of a migraine. It has also been theorized that certain physical and chemical agents act as triggers. Researchers know that migraines run in families, indicating a strong genetic component to the etiology, and although no specific genetic markers have been identified, some have been implicated.
The current thinking includes a theory by Moskowitz that involves the trigeminovascular complex, where neurons release substance P and nitric oxide causing neurogenic inflammation of the meninges causing the migraine headache and associated symptoms. (Alfredo Bianchi et al., Vitamins and Hormones, Vol. 69 2004 p. 297-312)
Migraineurs have been found to have lower magnesium levels in the red blood cells and brain during a migraine. A mitochondrial dysfunction resulting in impaired oxygen metabolism has been suggested for migraine pathogenesis. It has been reported that a defect of reduced NADH (nicotinamide adenine dinucleotide dehydrogenase) in the mitochondria as well as citrate synthase and cytochrome-c-oxidase platelet activity. Mitochondria play a dominant role during cellular respiration in the production of ATP (adenosine-5′-triphosphate) that is responsible for the transfer of energy by electron transport from cell to cell. This is done by oxidizing the major products of glucose, pyruvate, and NADH. Some studies have shown an impaired energy metabolism in brain and skeletal muscle in migraine patients. Patients have demonstrated a reduction in mitochondrial phosphorylation potential in between attacks, further interfering with the cellular electron transport chain. (Bianchi, Id.)
Migraineurs who suffer from migraine with aura have a significant increase of total homocysteine in cerebrospinal fluid compared to the normal population. (Isobe and Terayama, Headache: J Head and Face Pain, Vol. 50 No. 10 p 1561-1569.) Hyperhomocysteinemia is a medical condition characterized by a high levels of homocysteine, which may lead to an excessive production of homocysteic acid, a toxin that possess strong excitatory effects on neurons. Homocysteic acid could sensitize the cerebral arteries and active the trigeminovascular system, predisposing a patient to migraine attacks. (Bianchi, Id.)
Many have proposed individual or combinations of dietary supplements as preventive treatment of migraines. Amir and Amir (U.S. Patent Application Publication 2004/0048870) propose a combination of magnesium in a range of 100 to 800 mg with 200 mg as preferred dosage and riboflavin in a range 100 to 600 mg with 400 mg as preferred dosage). Amir and Amir also propose combining magnesium and riboflavin with calcium, as well as a further combination with calcium and Vitamin D. Amir and Amir do not propose other vitamins, in particular other B vitamins, in combination with magnesium and riboflavin.
In U.S. Pat. No. 7,335,384, Khaled propose a combination of riboflavin, pyridoxine, cobalamin, magnesium, glucosamine sulfate, methylsulfonylmethane and coenzyme Q-10 in wide ranges of therapeutic levels in further combination with beta carotene, thiamine HCl, ascorbic acid, folate, biotin, vitamin E, zinc, selenium, manganese, glutathione, niacinamide, N-acetyl-tyrosine, α-lipoic acid, hydroxycitric acid, S-adenosylmethionine, pantothenic acid, and chondroitin sulfate for the prevention and treatment of migraine and other disease states and conditions associated with neurogenic inflammation.
In U.S. Pat. No. 6,500,450, Hendrix teaches an extract of the feverfew plant containing parthenolide in combination with magnesium, as a combination of magnesium oxide and a magnesium salt of an organic acid with or without riboflavin as a method of reducing the number of migraine headaches and associated symptoms. Previously in U.S. Pat. No. 6,068,999, Hendrix proposed that the ratio of the magnesium oxide to a magnesium salt of citric acid is 1:1 in combination with parthenolide, with or without riboflavin.
In U.S. Pat. No. 6,465,517, Van Der Zee proposes a composition comprising taurine, coenzyme Q10 and additionally creatine, L-carnitine, certain vitamins and minerals, carbohydrates, proteins, fats and herbal extracts for the treatment, not prevention of migraines. Van Der Zee does not include in the composition most water-soluble vitamins, only riboflavin, thiamine and ascorbic acid.
Piper has proposed in U.S. Pat. No. 6,159,505 several compositions and methods for the treatment and prevention of migraine or stress headaches. Piper teaches a combination of potassium, magnesium and pyridoxine (Vitamin B6) and optionally further combines the magnesium and pyridoxine ingredients with other common vitamins and minerals in a typical multivitamin preparation and still further adds a simple analgesic to the method of treatment.
While these compositions and methods may be suitable for the particular purpose employed, or for general use, they would not be as suitable for the purposes of the present invention as disclosed hereafter.